2-methoxy-3, 5-dichloro-6-nitro-benzoates



3,l3,d53 Patented Dec. 12, I951 This invention relates to new herbicidalcompositions of matter. More specifically, this invention relates to thecontrol of undesirable plant life with2-methoxy-3-5-dichloro-6-nitrobenzoic acid, its anhydride, it amides,its esters, its alkali metal salts, or its amine salts. 2-methoxy-3-5-dichloro-6-nitrobenzoic acid which has the structure IC O H OzN- -00H:

will hereinafter be referred to as compound I. This chemical compoundand its derivatives as cited above have marked activity as herbicidesuseful for the control of undesirable plant life.

Compound I can be prepared readily, for example, from the known compound3,5-dichlorosalicylic acid. This compound is first nitrated by treatingit with concentrated nitric acid in the presence of fuming sulfuricacid. The reaction proceeds satisfactorily at room temperature, and thereaction mixture is poured into ice water to isolate the desired3.,5-dichloro-6-nitrosalicylic acid. The nitro compound is thenmethylated by treating it as its alkali metal salt with an excess ofdimethyl sulfate. The dimethyl sulfate is preferably added with coolingof the reaction mixture, but the reaction is completed by refluxing thereaction mixture, which is then treated with an aqueous solution ofalkali metal hydroxide and again refluxed to hydrolyze any carboxylicacid ester which may have formed. The cooled reaction mixture isacidified with a mineral acid such as hydrochloric acid, and theprecipitated solid is filtered off and washed with cold water. Thecompound I obtained in this manner is suitable for many herbicidal usesas such, but if desired it can be purified, for example, byrecrystallization from a suitable solvent.

The anhydride of compound I is prepared by the removal of one moleculeof water from two molecules of compound I as the free acid. In practice,it is convenient to prepare the anhydride by the acylation of the freecarboxylic acid by its acid halide in the presence of a strong acylatingagent such as pyridine. Thus a mixture of dry pyridine and dry benzeneare treated with 1 mole of the acid chloride of compound I. The slightlyexothermic reaction proceeds with the formation of an intermediatepyridinium salt. One mole of co pound I as the free acid is then added,the precipitate of pyridine hydrochloride is removed, and the anhydrideof compound I is isolated by removal of the benzene.

The acid halide of compound I required in the above and other synthesesis prepared by the reaction of the free acid with a phosphorus trihalidein the conventional manner. Thus the treatment of compound I withphosphorus trichloride until the reaction ceases produces the acidchloride of compound I.

Compounds which are salts, esters, or amides of compound I can beprepared readily from the free acid. Thus treatment of the free acidwith ammonium hydroxide gives a product which is the salt ammonium2-methoxy-3,5-dichloro-6-nitrobenzoate. Similarly, an alkali metal saltof compound I can be made by the treatment of the free acid with bases,such as the hydroxides, of alkali metals. Treatment of the acid withsodium hydroxide thus gives the salt sodium2-methoxy-3,5-dichloro-6-nitrobenzoate as the product, while the use ofpotassium hydroxide gives the salt potassium2-methoxy-3,5-dichloro-6-nitrobenzoate.

Amine salts of compound I are prepared by the addition of the free acidto various amines. Typical amines which can be used to prepare suchamine salts are dimethylamine, trimethylamine, triethylamine,diethanolamine, triethanolamine, isopropylamine, morpholine, and thelike. The resulting products are, respectively, the dimethylamine,trimethylamine, triethylamine, diethanolamine, triethanolamine,isopropylamine, and morpholine salts of2-methoxy-3,S-dichloro-6-nitrobenzoic acid.

Esters of compound I are prepared by the condensation of the acid withvarious alcohols. Thus the condensation of methyl alcohol with compoundI gives the desired ester, methyl2-methoXy-3,5-dichloro-6-nitrobenzoate. Other typical alcohols which canbe used are propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl,amyl, hexyl, heptyl, octyl, nonyl, decyl, and the like. The products arethe corresponding alkyl esters of Z-methoxy- 3,5-dichloro-6-nitrobenzoicacid. Although such complex esters as those prepared by theesterification of compound I with butoxyethanol, propylene glycol butylether, and the like are useful products in accordance with thisinvention, preferred esters are those in which the esterifying group isan unsubstituted alkyl group which contains from 1-to 10 carbon atoms.The condensation of the acid with the alcohol is carried out suitably inan inert solvent such as an aromatic hydrocarbon and in the presence ofa few percent by weight of an acid catalyst such as p-toluenesulfonicacid. The water which forms during the esterification reaction can beremoved continuously in many cases from the reaction mixture bydistillation as it forms, and its volume can be measured to determinewhen the esterification is complete. The ester is then isolated bydistillation of the inert solvent.

Amides of compound I can be prepared conveniently by the reaction of theacid halide of compound I with ammonia or various amines. The reactioncan be carried out in an inert solvent such as ether or benzene.Preferably two moles of the amines are used for each mole of the acidhalide employed, since the hydrogen halide released during the reactionis taken up by some of the free amine which remains.

action of the acid chloride of compound I with ammonia, either as thefree gas or as an aqueous solution. This amide can also be prepared byhydrolysis of the corresponding nitrile. Substituted amides are preparedby the reaction of the acid halide of compound I with amines such as anyof the primary or secondary amines suggested above for the preparationof the amine salts of compound I. Thus, for example, the reaction of theacid chloride of compound I with methylarnine, butylamine, decylamine,or diethylamine gives the N-methyl-, N-butyl-, N-decyl-, orN,N-diethyl-2-methoxy-3,5-dichloro-6-nitrobenzamides, respectively.While more complex amines such as the aromatic amines can be used as theamine reactant to give desirable products, which are specifically.

named as anilides, preferred amine reactants are alkylamines containingup to 10 carbon atoms.

For practical use as herbicides, the'compounds of this invention areformulated with inert carriers to obtain proper concentrations and tofacilitate handling. For example, these compounds can be formulated intodusts by combining them with such inert substances as talc or clays. Thealkali metal salts of compound I are par ticularly suited tosuch dustformulations, and dusts containing from 5 to 25 percent by weight ofactive. compound are convenient for use in the field. The compounds Thesimplest amide, 2-methoXy- 3,5dichloro-o-nitrobenzamide, can be preparedby the reor this invention, however, are preferably applied as sprays.These can be made as simple solutions by dissolving the compounds inorganic solvents such as xylene, kerosene, or the methylatednaphthalenes. The esters of compound I, which ordinarily are liquids atroom temperature, are particularly suited to formulation by this method.The amine salts of compound I often show good solubility in water andcan be used directly as aqueous solutions.

The compounds of this invention can also be emulsified or suspended inwater by the addition of emulsifiers and wetting agents. Theformulations of these active herbicidal compounds are either applieddirectly to the plants to be controlled, or the soil in which the plantsare growing can be treated. Substances such as other pesticides,stabilizers, activators, synergists, spreaders and adhesives can beadded to the formulations if desired. There is no significant differencein effect from the amount of water or organic solvent for diluting theseherbicides, providing the same amount of chemical is distributed evenlyover a given area. Such distribution can be obtained, for example, withlow-pressure, low-volume sprays at the rate of about gallons of sprayper acre.

In applying the herbicidal compounds, consideration must be given to thenature and stage of growth of the crop, the species of weeds present,the stage of growth of the weeds, environmental factors influencing therate and vigor of the weed growth, Weather conditions at the time ofapplication and immediately following, and the dosage to be applied to agiven area. Weeds are most susceptible when they are small and growingrapidly. Early application, therefore, results in better control withless chemical and increased yields because of the early destruction ofthe competing weeds. The larger and older the weeds the higher theconcentration needed to kill them. Summer annuals such aslambs-quarters, pigweeds, cocklebur, and sunflower should be sprayedwhen they are less than 4 inches high. Winter annuals such as variousmustards, fan-weed, yellow star-thistle, and wild radish are most easilykilled while they are still in the rosette stage. Usually weeds growingrapidly under optimum conditions are relatively susceptible, whereasthose growing under adverse conditions tend to be resistant to theherbicide sprays.

The effectiveness of the compounds of this invention in small quantitiesmakes them economically sound for weed control on large areas, with agreat saving in labor and cost, in addition to corresponding cropincreases. These compounds are particularly valuable in weed controlbecause they are harmful to many weeds but harmless or relativelyharmless to some cultivated crops. Minute quantities in contact withplant tissues may be absorbed and translocated to all parts of theplant, causing striking changes in the form and functions and oftenresulting in their death. The actual amount of compound to be useddepends on a variety of factors but is influenced primarily by thespecies of undesirable plant to be controlled. Thus while fractions of apound of actual compound I or its equivalent of an ester, salt, amide,or the anhydride of compound I are often suflicient for post-emergenceweed control on an acre of corn, seed flax, perennial grass seed crops,pastures or grazing areas (without legumes), wheat, and the like, theparticular species of weeds encountered in evergreen and deciduousdormant nursery stock, nursery conifers, waste areas, woody brush, andthe like may require the use of one or more pounds of compound I or itsderivatives per acre for good control. Dosage adjustments with thelow-volume, low-pressure applications suggested can be made by changingthe nozzle size, nozzle spacing, pressure, or traveling rate of thespray equipment.

The manner in which the herbicidal compounds of this invention can beprepared and utilized is illustrated in the following examples:

4 EXAMPLE 1 Preparation of 3,5-dicltlor0-6-nitrosalicylic acid3,5-dichlorosalicylic acid (30.0 g.), which can be obtained, for exampleas described by Leulier and Pinet in the Bull. soc. chim., vol. 41, page1363 (1927), is mixed with g. of 20% fuming sulfuric acid in a 250-ml.,round-bottomed flask fitted with a mechanical stirrer and droppingfunnel. The mixture is stirred vigorously while a mixture of 25 g. ofconcentrated nitric acid and 30 g. of 20% fuming sulfuric acid is addeddropwise. The mixture is allowed to stand overnight and is then pouredslowly with stirring into 2 liters of ice water. The solid is filtered,washed with cold water, pressed dry, and dried completely in a vacuumoven to give the desired 3,5-dichloro--nitrosalicylic acid.

EXAMPLE 2 Preparation of Z-methoxy-3,5-dichlo-ro-6-nitrobenzoic acid(compound I 3,S-dichloro-6-nitrosalicylic acid (0.87 mole) is dissolvedin a solution of sodium hydroxide (139 g.; 3.48 moles) in 900 m1. ofwater in a 2-liter, round-bottomed flask fitted with a reflux condenser,mechanical stirrer, internal thermometer, and dropping funnel. Thesolution is cooled to 20 C., and dimethyl sulfate (219 g.; 1.74 moles)is added to the vigorously stirred solution. The mixture is stirred for20 minutes while the temperature is maintained below 35 C. by icecooling. Another portion of dimethyl sulfate (139 g.) is added, and themixture is stirred for 10 minutes while the temperature is maintainedbelow 45 C. The mixture is then stirred and refluxed for 2 hours,treated with a solution of 69.6 g. (1.74 moles) of sodium hydroxide in250 ml. of water, and refluxed for an additional 2 hours. The cooledreaction mixture is acidified to Congo red with hydrochloric acid. Theprecipitated solid is filtered, washed with cold water, pressed dry, anddried completely in a vacuum oven to give compound I.

EXAMPLE 3 Preparation of the sodium salt of compound I Compound I (0.5mole) is dissolved in 500 cc. of methanol and treated with a solution ofsodium hydroxide (20 g.; 0.5 mole) in 100 cc. of methanol. The methanolis removed by distillation in vacuo on the steambath, and the solidresidue is slurried with 100 cc. of cold, dry ether, filtered, presseddry, and dried completly in a vacuum oven to give the desired sodiumsalt of compound 1.

EXAMPLE 4 Preparation of the ammonium salt of compound 1 Treatment ofcompound I (0.5 mole) in 500 cc. of methanol with 34 cc. of commercialconcentrated ammonium hydroxide according to the method given in theprevious example gives the desired ammonium salt of compound 1.

EXAMPLE 5 Preparation of the dimethylamine salt of compound 1 Compound I(0.5 mole) is dissolved in 500 cc. of dry ether and treated withdimethylamine (22.5 g.; 0.5 mole). The solid which separates isfiltered, washed twice with 100 cc. portions of cold ether, filtered,pressed dry, and dried completely in a vacuum oven to give the desireddimethylamine salt of compound 1.

EXAMPLE 6 Preparation of the diethanolamine salt 0 compound I In themanner described in the previous example, compound I (0.5 mole) istreated with diethanolamine (52.5 g.; 0.5 mole) in 500 cc. of dry ether.The product which is isolated is the diethanolamine salt of compound I.

EXAMPLE 7 Preparation of the morpholine salt of compound 1 Preparationof the ethyl ester of compound I Compound I (0.5 mole), ethyl alcohol(23 g.; 0.5 mole), and 3.0 g. of -p-toluenesulfonic acid are dissolvedin 500 ml. of benzene, and the solution is placed in a 1 liter,round-bottomed flask fitted with a reflux condenser and a calibratedDean-Stark tube. The solution is heated at reflux temperature until 9cc. of water have been collected in the Dean-Stark tube. The cooledreaction mixture is then extracted twice with 50-cc. portions of 10%sodium carbonate solution, and filtered. The benzene is distilled off invacuo on the steam bath, and the residue is then distilled in vacuo togive the desired ethyl ester of compound 1.

EXAMPLE 9 Preparation of the decyl ester-of compound I In the manner andapparatus described in the previous example, compound I (0.5 mole) andnormal primary decyl alcohol (79 g.; 0.5 mole) are refluxed in 500 ml.

of benzene in the presence of 3.0 g. of p-toluenesulfouic EXAMPLE 10Preparation of the n-butyl ester of compound I The reaction of compoundI (0.5 mole) and n-butyl alcohol (37 g.; 0.5 mole) by the methoddescribed above for the preparation of the ethyl ester is used toprepare the n-butyl ester of compound I.

EXAMPLE 11 Preparation of the acid chloride of compound I Compound I (1mole) is placed with 500 cc. of dry benzene in a 2-liter, 3-necked,round-bottomed flask fitted with a mechanical stirrer, reflux condenser(calcium chloride tube), and dropping funnel. Phosphorus trichloride(123 g.; 0.9 mole) is added slowly dropwise with vigorous stirring whilethe reaction flask is cooled with cold water if necessary to control thereaction. When all the PO1 has been added and the evolution of hydrogenchloride has ceased, the reaction mixture is then transferred todistillation apparatus, and the solvent is distilled off. The residue isthen distilled in vacuo to give the desired acid chloride of compound I.

EXAMPLE 12 Preparation of the amide of compound I One mole of the acidchloride of compound I is placed with 500 cc. of dry benzene in a1-liter, 3-necked flask fitted with a reflux condenser, mechanicalstirrer, and a gas inlet tube having a sparger tip. The mixture isstirred while dry ammonia gas is passed into the mixture for severalhours. When the ammonia gas is no longer taken up, the precipitated saltis filtered oh? and extracted twice with 100 ml. portions of ether. Theether extracts and benzene filtrate are dried over magnesium sulfate andfiltered, and the solvents are distilled off to give the desired amideof compound 1.

EXAMPLE 13 Preparation of the N-n-decylamide of compound I One mole ofthe acid chloride of compound I and 500 ml. of dry benzene are placed ina 2-liter, S-necked, roundamine has been added, the reaction bottomedflask fitted with a mechanical stirrer, reflux condenser, internalthermometer, and dropping funnel. n-Decylamine (314 g.; 2.0 moles) in250 ml. benzene is added dropwise with vigorous stirring. When all themixture is refluxed for 2 hours and cooled, after which the precipitatedsalt is filtered off and extracted with two ml. portions of ether. Theether extracts and benzene filtrate are dried over magnesium sulfate andfiltered. Distillation of the solvents gives the desired N-n-decylamideof compound I.

EXAMPLE 14 Preparation of the N,N-diethylam'ide of compound I One moleof the acid chloride of compound I is treated with diethylamine (146 g.;2.0 moles) in the manner and apparatus described in the previous exampleto give the N,N-diethylamide of compound I.

EXAMPLE 15 Preparation of the anhydride of compound I Dry pyridine (158g.; 2.0 moles) and 1 liter of dry benzene are placed in a 2-liter,3-necked, round-bottomed flask fitted with a dropping funnel, mechanicalstirrer, reflux condenser, and internal thermometer. One mole of theacid chloride of compound I, which is prepared as described in aprevious example, is added rapidly with stirring to the reactionmixture. Compound I (1 mole) is then added in portions over a period ofabout 10 minutes with rapid stirring. The pyridine hydrochloride whichprecipitates is filtered off, and the benzene is distilled from thefiltrate in vacuo. The residue contains the desired anhydride ofcompound I, which can be purified by crystallization from a suitablesolvent.

EXAMPLE 16 Preparation of an emulsifiable concentrate of compound I Thefollowing concentrate is prepared by mixing the ingredients intimatelyin the given percentage proportions Antarox A-400 the trade name underwhich a noni'onic detergent of the aromatic polyethylene glycol othertype is sold. The above concentrate is diluted with water to the desiredconcentration for use.

EXAMPLE 17 Preparation of an emulsifiable concentrate of the n-butylester of compound I The following ingredients are mixed thoroughly inthe given percentage proportions by weight:

Percent n-Butyl ester of compound I 59 Xylene 10 Triton X-100 5 Kerosene26 Triton X-100 is the trade name under which an emulsifier of the alkylaryl polyether alcohol type is sold. The above concentrate is dilutedwith water to the desired concentration for use.

EXAMPLE 18 Preparation of a dust from the sodium salt of compound I byweight) for experimental purposes in greenhouses, and its response tochemicals is very similar to that observed for a wide variety ofeconomically important species of undesirable plant life in the field.

The herbicidal activity of the compounds of this invention, for example,can be demonstrated in greenhouse experiments on young potted tomatoplants (Bonny Best variety). The compounds are formulated into 10percent wettable powders and are dispersed in waterat a concentration of2,000 parts per million actual chemical. Ten milliliters of an aliquotportion of the dispersion is added to the soil surface of the tomatoplants, approximately 5 to 7 inches tall. In order to avoid undueconcentration o-r accumulation of the chemical in any given area, 5holes the size of a pencil and about 1 inch deep are punched in the soilsurface around the shoot, and the 10 milliliter application is dividedequally among the 5 holes. Three plants are used for each application.The treated plants are held under greenhouse conditions for 7 days,provided with subterranean watering, and observed for response totreatment. The results indicate a high order of'herbicidal toxicity ofthe compounds of this invention.

I claim as my invention:

1. A compound selected from the group consisting of2-methoxy-3,5-dichloro-6-nitrobenzoic acid, its anhydride, its alkalimetal salts, its ammonium salt, its morpholine salt, its alkyl aminesalts-in which the amine component is an unsubstituted alkyl amine of upto six carbon atoms, its alkanol amine salts in which the aminecomponent is an unsubstituted alkanol amine of up to six carbon atoms,its esters in which the esterifying group is an unsubstituted alkylgroup of from one to ten carbon. atoms, its butoxyethanol ester, itsunsubstituted amide, and its alkyl amides in which the amine componentis an unsubstituted alkyl amine of up to ten carbon atoms.

2. An alkali metal salt of 2-methoxy-3,5-dichloro-6- nitrobenzoic acid.

3. An alkyl amine salt of 2-methoxy-3,5-dichloro-6- nitrobenzoic acid inwhich the amine component is an unsubstituted alkyl amine of up to sixcarbon atoms.

4. An ester of 2-methoxy-3,5 dichloro-6-nitrobenzoic 5 acid, in whichthe esterifying group is an unsubstituted alkyl group of from one to tencarbon atoms.

5. An alkyl amide of 2-methoxy-3,5-dichloro6-nitrobenzoic acid in whichthe amine component is an unsubstituted alkyl amine of up to ten carbonatoms.

10 6. An alkanol amine salt of 2-methoxy-3,5dichloro-6- nitrob'enzoicacid in which the amine component is an unsubstituted alkanol amine ofup to six carbon atoms.

7. The dimethvlamine salt of 2-methoxy-3,5-dichlor0-6- nitrobenzoicacid.

15 8. 2-methoxy-3,5-dichloro-6-nitro enzoic acid.

9. Sodium 2-methoxy-3,5-dicl1loro-6-nitrobenzoate.

10. The diethanola-mine salt of 2-methoxy,3,5-dichloro- 6-nitrobenzoicacid.

11. n-Butyl 2-methoXy-3,5-dichloro-6-nitrobenzoate.

2o 12. bis(2-methoxy-3,S-dichloro-6-nitrobenzoic) anhydride.

References Cited in the file of this patent UNITED STATES PATENTS 251,260,289 Adams at al Mar. 26, 1918 2,695,840 Leppla Nov. 30, 19542,726,947 Baumgartner Dec. 13, 1955 2,905,706 Sims et al. Sept. 22, 1959OTHER REFERENCES

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF2-METHOXY-3,5-DICHLORO-6-NITROBENZOIC ACID, ITS ANHYDRIDE, ITS ALKALIMETAL SALTS, ITS AMMONIUM SALT, ITS MORPHOLINE SALT, ITS ALKYL AMINESALTS IN WHICH THE AMINE COMPONENT IS AN UNSUBSTITUTED ALKUL AMINE OF UPTO SIX CARBON ATOMS, ITS ALKANOL AMINE SALTS IN WHICH THE AMINECOMPONENT IS AN UNSUBSTITUTED ALKANOL AMINE OF UP TO SIX CARBON ATOMS,ITS ESTERS IN WHICH THE ESTERIFYING GROUP IS AN UNSUBSTITUTED ALKYLGROUP OF FROM ONE TO TEN CARBON ATOMS, ITS BUTOXYETHANOL ESTER, ITSUNSUBSTITUTED AMIDE, AND ITS ALKYL AMIDES IN WHICH THE AMINE COMPONENTIS AN UNSUBSTITUTED ALKYL AMINE OF UP TO TEN CARBON ATOMS.
 4. AN ESTEROF 2-METHOXY-3,5-DICHLORO-6-NITROBENZOIC ACID, IN WHICH THE ESTERIFYINGGROUP IS AN UNSUBSITUTED ALKYL GROUP OF FROM ONE TO TEN CARBON ATOMS.